Remarkably, 2m of linear DNA must be packaged into to the small confines of the nucleus. To ensure proper cell state, each cell must organize its DNA, RNA, and proteins within the nucleus in ways that differ in each cell type. More than 25 years ago, it had been suspected that RNA itself might be a key organizing factor that shapes this dynamic nuclear floor plan. Indeed, many lncRNAs (e.g. XIST, FIRRE, NEAT1) play important roles in maintaining and establishing nuclear domains.
We are applying single molecule RNA FISH, live cell imaging and CRISPR-Display technology to understand how lncRNAs facilitate intra- and inter-chromosomal interactions both spatially and temporally.